Summary: nature neurOSCIenCe VOLUME 13 | NUMBER 3 | MARCH 2010 369
a r t I C l e S
A fundamental approach of systems neuroscience is to probe the brain
with repeated stimulus trials and infer neural mechanism from the
recorded responses. Extracellularly recorded responses are typically
analyzed by computing the average spike rate across trials. By averag-
ing, the experimenter hopes to overcome the apparent noisiness of
spiking and estimate the true change in the neuron's underlying firing
rate. It is probably true that much of the recorded spiking variability is
effectively noise and doesn't reflect fundamentally different responses
on different trials. However, it is clear that the neural response can
vary meaningfully across trials. For example, the neural state may be
initially similar across trials but become variable in response to a
stimulus1.Alternately, sensory cortex can be restless and active2 before
stimulus onset. A central question is whether the stimulus-driven
response suppresses such ongoing variability3­5, superimposes with
it2,6,7 or yields even greater variability as a result of nonlinear inter-
actions8? In general, does stimulus onset drive variability up (result-
ing from the variable responses themselves) or down (resulting from
suppression of variable ongoing activity)?